A Multigene Signature Based on Cell Cycle Proliferation Improves Prediction of Mortality Within 5 Yr of Radical Nephrectomy for Renal Cell Carcinoma

Todd M. Morgan, Rohit Mehra, Placede Tiemeny, Stuart Wolf, Shulin Wu, Zaina Sangale, Michael Brawer, Steven Stone, Chin Lee Wu, Adam S. Feldman

Research output: Contribution to journalArticle

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Abstract

Background: There is a critical need for improved prognostic discrimination in patients with renal cell carcinoma (RCC) given the increasing awareness that some patients may be managed with active surveillance, while others with higher-risk disease might benefit from adjuvant therapy following surgery. Objective: To determine whether a multigene proliferation signature predicts long-term oncologic outcomes in surgically resected RCC. Design, setting, and participants: The cell cycle proliferation (CCP) score was determined after radical nephrectomy for localized clear cell, papillary, or chromophobe RCC in 565 patients. Outcome measurements and statistical analysis: The primary end point was disease-specific mortality (DSM), and disease recurrence was a secondary end point. Association with outcomes was evaluated by Cox proportional hazards survival analysis. The CCP score was compared with the Karakiewicz nomogram, and a composite (R-CCP) score was developed. Results and limitations: A total of 68 patients (12%) recurred and 32 (6%) died of disease within 5 yr of nephrectomy. The CCP score was an independent predictor of recurrence (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.07–2.09) and DSM (HR 2.49, 95% CI 1.53–4.04) after adjusting for clinical variables using the baseline nomogram. The composite R-CCP score gave a Harrell's concordance index of 0.87 and stratified patients into low- (n = 338) and high-risk (n = 202) categories with 99% and 84% cancer-specific survival probabilities, respectively (p < 0.001). Conclusions: The CCP score is a significant, independent predictor of long-term oncologic outcomes in patients who have undergone nephrectomy for RCC. Combining the molecular classifier with baseline clinical variables allows for accurate, patient-specific risk assessment for use in guiding clinical management. Patient summary: In this study, we sought to understand how well gene expression information from individual kidney tumors can predict cancer recurrence and death following surgical removal. We found that the combination of the gene expression test and clinical characteristics provides an accurate prognostic assessment to help inform clinical decisions. A previously established, tissue-based molecular classifier predicted recurrence and mortality after radical nephrectomy, adding prognostic information beyond a validated clinical nomogram. A composite clinical and molecular score was developed, which accurately categorized patients according to their likelihood of mortality.

LanguageEnglish (US)
Pages763-769
Number of pages7
JournalEuropean Urology
Volume73
Issue number5
DOIs
StatePublished - May 1 2018

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Nephrectomy
Renal Cell Carcinoma
Cell Cycle
Cell Proliferation
Mortality
Nomograms
Recurrence
Confidence Intervals
Gene Expression
Neoplasms
Survival Analysis
Kidney
Survival

Keywords

  • Biomarkers
  • Kidney cancer
  • Molecular classifier
  • Predictive models
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Urology

Cite this

A Multigene Signature Based on Cell Cycle Proliferation Improves Prediction of Mortality Within 5 Yr of Radical Nephrectomy for Renal Cell Carcinoma. / Morgan, Todd M.; Mehra, Rohit; Tiemeny, Placede; Wolf, Stuart; Wu, Shulin; Sangale, Zaina; Brawer, Michael; Stone, Steven; Wu, Chin Lee; Feldman, Adam S.

In: European Urology, Vol. 73, No. 5, 01.05.2018, p. 763-769.

Research output: Contribution to journalArticle

Morgan, Todd M. ; Mehra, Rohit ; Tiemeny, Placede ; Wolf, Stuart ; Wu, Shulin ; Sangale, Zaina ; Brawer, Michael ; Stone, Steven ; Wu, Chin Lee ; Feldman, Adam S. / A Multigene Signature Based on Cell Cycle Proliferation Improves Prediction of Mortality Within 5 Yr of Radical Nephrectomy for Renal Cell Carcinoma. In: European Urology. 2018 ; Vol. 73, No. 5. pp. 763-769.
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abstract = "Background: There is a critical need for improved prognostic discrimination in patients with renal cell carcinoma (RCC) given the increasing awareness that some patients may be managed with active surveillance, while others with higher-risk disease might benefit from adjuvant therapy following surgery. Objective: To determine whether a multigene proliferation signature predicts long-term oncologic outcomes in surgically resected RCC. Design, setting, and participants: The cell cycle proliferation (CCP) score was determined after radical nephrectomy for localized clear cell, papillary, or chromophobe RCC in 565 patients. Outcome measurements and statistical analysis: The primary end point was disease-specific mortality (DSM), and disease recurrence was a secondary end point. Association with outcomes was evaluated by Cox proportional hazards survival analysis. The CCP score was compared with the Karakiewicz nomogram, and a composite (R-CCP) score was developed. Results and limitations: A total of 68 patients (12{\%}) recurred and 32 (6{\%}) died of disease within 5 yr of nephrectomy. The CCP score was an independent predictor of recurrence (hazard ratio [HR] 1.50, 95{\%} confidence interval [CI] 1.07–2.09) and DSM (HR 2.49, 95{\%} CI 1.53–4.04) after adjusting for clinical variables using the baseline nomogram. The composite R-CCP score gave a Harrell's concordance index of 0.87 and stratified patients into low- (n = 338) and high-risk (n = 202) categories with 99{\%} and 84{\%} cancer-specific survival probabilities, respectively (p < 0.001). Conclusions: The CCP score is a significant, independent predictor of long-term oncologic outcomes in patients who have undergone nephrectomy for RCC. Combining the molecular classifier with baseline clinical variables allows for accurate, patient-specific risk assessment for use in guiding clinical management. Patient summary: In this study, we sought to understand how well gene expression information from individual kidney tumors can predict cancer recurrence and death following surgical removal. We found that the combination of the gene expression test and clinical characteristics provides an accurate prognostic assessment to help inform clinical decisions. A previously established, tissue-based molecular classifier predicted recurrence and mortality after radical nephrectomy, adding prognostic information beyond a validated clinical nomogram. A composite clinical and molecular score was developed, which accurately categorized patients according to their likelihood of mortality.",
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AU - Morgan, Todd M.

AU - Mehra, Rohit

AU - Tiemeny, Placede

AU - Wolf, Stuart

AU - Wu, Shulin

AU - Sangale, Zaina

AU - Brawer, Michael

AU - Stone, Steven

AU - Wu, Chin Lee

AU - Feldman, Adam S.

PY - 2018/5/1

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N2 - Background: There is a critical need for improved prognostic discrimination in patients with renal cell carcinoma (RCC) given the increasing awareness that some patients may be managed with active surveillance, while others with higher-risk disease might benefit from adjuvant therapy following surgery. Objective: To determine whether a multigene proliferation signature predicts long-term oncologic outcomes in surgically resected RCC. Design, setting, and participants: The cell cycle proliferation (CCP) score was determined after radical nephrectomy for localized clear cell, papillary, or chromophobe RCC in 565 patients. Outcome measurements and statistical analysis: The primary end point was disease-specific mortality (DSM), and disease recurrence was a secondary end point. Association with outcomes was evaluated by Cox proportional hazards survival analysis. The CCP score was compared with the Karakiewicz nomogram, and a composite (R-CCP) score was developed. Results and limitations: A total of 68 patients (12%) recurred and 32 (6%) died of disease within 5 yr of nephrectomy. The CCP score was an independent predictor of recurrence (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.07–2.09) and DSM (HR 2.49, 95% CI 1.53–4.04) after adjusting for clinical variables using the baseline nomogram. The composite R-CCP score gave a Harrell's concordance index of 0.87 and stratified patients into low- (n = 338) and high-risk (n = 202) categories with 99% and 84% cancer-specific survival probabilities, respectively (p < 0.001). Conclusions: The CCP score is a significant, independent predictor of long-term oncologic outcomes in patients who have undergone nephrectomy for RCC. Combining the molecular classifier with baseline clinical variables allows for accurate, patient-specific risk assessment for use in guiding clinical management. Patient summary: In this study, we sought to understand how well gene expression information from individual kidney tumors can predict cancer recurrence and death following surgical removal. We found that the combination of the gene expression test and clinical characteristics provides an accurate prognostic assessment to help inform clinical decisions. A previously established, tissue-based molecular classifier predicted recurrence and mortality after radical nephrectomy, adding prognostic information beyond a validated clinical nomogram. A composite clinical and molecular score was developed, which accurately categorized patients according to their likelihood of mortality.

AB - Background: There is a critical need for improved prognostic discrimination in patients with renal cell carcinoma (RCC) given the increasing awareness that some patients may be managed with active surveillance, while others with higher-risk disease might benefit from adjuvant therapy following surgery. Objective: To determine whether a multigene proliferation signature predicts long-term oncologic outcomes in surgically resected RCC. Design, setting, and participants: The cell cycle proliferation (CCP) score was determined after radical nephrectomy for localized clear cell, papillary, or chromophobe RCC in 565 patients. Outcome measurements and statistical analysis: The primary end point was disease-specific mortality (DSM), and disease recurrence was a secondary end point. Association with outcomes was evaluated by Cox proportional hazards survival analysis. The CCP score was compared with the Karakiewicz nomogram, and a composite (R-CCP) score was developed. Results and limitations: A total of 68 patients (12%) recurred and 32 (6%) died of disease within 5 yr of nephrectomy. The CCP score was an independent predictor of recurrence (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.07–2.09) and DSM (HR 2.49, 95% CI 1.53–4.04) after adjusting for clinical variables using the baseline nomogram. The composite R-CCP score gave a Harrell's concordance index of 0.87 and stratified patients into low- (n = 338) and high-risk (n = 202) categories with 99% and 84% cancer-specific survival probabilities, respectively (p < 0.001). Conclusions: The CCP score is a significant, independent predictor of long-term oncologic outcomes in patients who have undergone nephrectomy for RCC. Combining the molecular classifier with baseline clinical variables allows for accurate, patient-specific risk assessment for use in guiding clinical management. Patient summary: In this study, we sought to understand how well gene expression information from individual kidney tumors can predict cancer recurrence and death following surgical removal. We found that the combination of the gene expression test and clinical characteristics provides an accurate prognostic assessment to help inform clinical decisions. A previously established, tissue-based molecular classifier predicted recurrence and mortality after radical nephrectomy, adding prognostic information beyond a validated clinical nomogram. A composite clinical and molecular score was developed, which accurately categorized patients according to their likelihood of mortality.

KW - Biomarkers

KW - Kidney cancer

KW - Molecular classifier

KW - Predictive models

KW - Renal cell carcinoma

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